Lubiprostone和肠易激综合征

肠易激综合征是一种常见的功能性胃肠道疾病,便秘型IBS因其症状顽固且无特效药物治疗引起更多关注。Lubiprostone(商品名Amitiza)是一种新型2型氯离子通道激活剂,此通道激活可以促进富含氯离子的组织间液和水转移至肠腔,增加肠腔内容物的容积,刺激和加速肠道转运,缓解便秘型IBS患者的症状。临床应用显示Lubiprostone是治疗慢性便秘和便秘型IBS安全、有效的药物。

Lubiprostone vs Senna in postoperative orthopedic surgery patients with opioid-induced constipation:A double-blind,active-comparator trial

AIM:To investigate the efficacy of lubiprostone compared to Senna on bowel symptoms and constipation in post-operative orthopedic patients treated with opioids.METHODS:In this double blind,randomized,active comparator trial,adults who required opioids for analgesia following orthopedic procedures and who were admitted in inpatient rehabilitation were randomized following baseline assessments to lubiprostone(Amitza),orally twice aday or Senna(generic)two capsules administered daily for six days.Subjects were assessed using the patient assessment of constipation(PAC)-symptoms(PAC-SYM)and the PAC-quality of life(PAC-QOL)scales measured at baseline and Day 7;Subjects were assessed daily for secondary measures included the Bristol stool scale bowel consistency,specific bowel symptom score(Nausea,cramping,straining,completeness,abdominal pain,time per lavatory attempt,assistance needed),adverse events and rescue medications required.Function was measured using the functional independence measure(FIM)at admission and discharge;length of stay(LOS)and missed treatments due to gastrointestinal symptoms were also assessed.RESULTS:64 adults were enrolled;56 participants(28 in each group)had baseline and follow up measures and were included in the intention to treat(ITT)analyses.43 participants completed the study,21 in the active lubiprostone and 22 in the active Senna group.The mean age of the participants was 71.5years(SD=11.4 years,range:28-96 years).In the ITT analyses,participants showed significant improvement in bowel symptoms as measured by the PACSYM(mean±SD,-0.28±0.60,range:-1-2.33)and PAC-QOL(mean±SD,0.33±0.81,range:-1.5-2.0)over time,but there were no significant differences between the lubiprostone and Senna groups in mean change in the PAC-SYM(-0.20±0.60 vs-0.36±0.61,P=0.61 respectively)or the PAC-QOL(0.29±0.76 vs0.37±0.87,P=0.61 respectively).The mean change in each bowel symptom also did not significantly differ between treatment groups on ITT analyses,except for completeness of bowel movement,with the Senna group showing greater negative mean change in bowel movement completeness(-0.56±1.01 vs-2.00±1.41,P=0.03)and for reduction of abdominal pain,favoring Senna(-0.14±0.73 vs-0.73±1.08,P=0.04).Fifteen(75%)participants in the lubiprostone and in the Senna group requested rescue treatments.Participants made significant functional improvement from admission to discharge over a median LOS of 12 d,with a mean FIM change of 29.13±13.58 and no significant between group differences(27.0±9.2 vs 31.5±16.6,P=0.27).CONCLUSION:Both lubiprostone and Senna improved constipation-related symptoms and QOL in opioid-induced constipation,with no significant between-group differences.

Lubiprostone used with polyethylene glycol in diabetic patients enhances colonoscopy preparation quality

AIM: To assess the additive effect of lubiprostone on the quality of colon preparation in diabetics given single-dosed polyethylene glycol electrolyte(PEG)for colonoscopy.METHODS:This was an investigator-initiated,singlecenter,single-blinded prospective trial comparing the efficacy of L+PEG to PEG alone on colon preparation quality in diabetics undergoing screening colonoscopy.The study was approved by our institution’s IRB.The PEG was given as a single-dose to address patientcompliance concerns voiced by our IRB with splitdosing.All patients received only clear liquids the day prior to colonoscopy.Experimental group(Grp L)received PEG+1 dose L 2 h prior to and 2 h after PEG completion.Control group(Grp C)received only PEG the evening prior to the colonoscopy.Patients were randomly assigned to one of the 2 groups.The endoscopist was blinded to which colon prep was given and all colonoscopies were complete.Upon colonoscopy completion,the endoscopist rated the colon prep-quality by a validated 5-point Likert scale(1-excellent to 5-inadequate).RESULTS:Sixty patients were enrolled in the study;30 Grp L and 30 Grp C.Overall,patients were excluded due to study non-completion in 12(41%)Grp L and 5(17%) Grp C,P=0.04.Average colon preparation score Grp L =2.47 and Grp C=3.00,P=0.09.Although this was not statistically significant,there was a trend towards improved colon prep in Grp L.Statistical significance may have been achieved if completion rates had been similar between both study groups.CONCLUSION:Use of 2-L capsules with PEG resulted in a trend towards improved colon prep over PEG alone in diabetic patients when given as a single-dose regimen.

Lubiprostone induced ischemic colitis

Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding.It is often multifactorial and more commonly encountered in the elderly.Several medications have been implicated in the development of colonic ischemia.We report a case of a 54-year old woman who presented with a two-hour history of nausea,vomiting,abdominal pain,and bloody stool.The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding.The radiologic,colonoscopic and histopathologic findings were all consistent with ischemic colitis.Her condition improved without any serious complications after the cessation of lubiprostone.This is the first reported case of ischemic colitis with a clear relationship with lubiprostone(Naranjo score of 10).Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

Lubiprostone:Clinical applications beyond constipation

In comparison to polyethylene glycol,lubiprostone offers other advantages and is increasingly being used as an adjunctive agent in diagnostic as well as management strategies not only in gastroenterology, but in other fields.For instance,lubiprostone exerts beneficial effects in cystic fibrosis tissues.It augmernts the chloride secretion in these cells by activating non-cystic fibrosis transmembrane regulator(CFTR) secretion of chloride by afflicted respiratory epithelia. Lubiprostone also seems to improve visualization of the gastrointestinal tract during procedures such as colonoscopy.This is especially true if the lubiprostone is administered prior to bowel cleansing with agents such as polyethylene glycol electrolyte(PEG-E). Lubiprostone also enhances and stimulates contraction in colonic as well as gastric muscles and may thus further contribute as a prokinetic agent.Besides these effects,lubiprostone also causes hyperpolarization in other tissues such as uterine muscle cells.This may prove to be of significant clinical benefit in the management of uterine pathologies in the near future.

Efficacy of Itopride in the Prevention of Lubiprostone-Induced Nausea

Background: The efficacy of lubiprostone for chronic constipation has been established through phase III clinical trials. Nevertheless, the continuation of lubiprostone therapy is reportedly difficult due to the development of nausea. The objective of this study is to determine whether the administration of itopride hydrochloride can reduce lubiprostone-related nausea. Methods: Two hundred and thirty-five patients who were receiving lubiprostone (24 μg capsule twice daily) were enrolled. Seventy-one patients took a prophylactic dose of itopride (50 mg tablet twice daily) together with lubiprostone to prevent nausea. Thus, the patients were divided into 2 groups: lubiprostone alone (164;control group) and combination therapy with lubiprostone and itopride (71;itopride group). Efficacy measures included changes in constipation scoring system scores, the incidence of treatment-related adverse events including nausea, and the percentage of patients who discontinued treatment within two weeks after administration. Results: Of the 235 patients who were enrolled, 196 were available for analysis. Both treatment groups experienced statistically significant improvements in constipation scoring system scores. The percentage of patients who reported ≥1 adverse event was significantly higher in the control group (40.9%) than in the itopride group (21.9%). The percentage of patients experiencing nausea was statistically and significantly lower in the itopride group than in the control group (9.4% versus 22.7%). The itopride regimen was also statistically superior compared to the control regimen in terms of treatment discontinuation. Conclusion: The prophylactic administration of itopride can decrease the risk of nausea in patients receiving lubiprostone and consequently reduce the risk of treatment discontinuation.

Lubiprostone用于治疗OBD的Ⅲ期研究结果

Sucampo制药公司已报道了其胃肠道用药lubiprostone（Ⅰ）用于治疗慢性非癌痛患者阿片引起的肠功能紊乱（OBD）的两项Ⅲ期研究的主要结果。

便秘药lubiprostone在美申请

Sucampo药物公司已经在美国提交了治疗慢性特发性便秘和有关症状的新药lubiprostone（Ⅰ）的申请。

Review of efficacy and safety of laxatives use in geriatrics

AIM:To study the efficacy and safety of pharmacolo-gical treatment of constipation in geriatrics.METHODS:Pub Med,MEDLINE,google scholar,and Ovid were searched to identify human studies performed on the use of laxatives in elderly with constipation,which were conducted between January1990 and January 2013 using the specified keywords.Controlled studies that enrolled geriatric patients with a diagnosis of constipation and addressed the efficacy and/or the safety of pharmacological treatments were included.Studies were excluded from this review if they were non-controlled trials,case series,or case reports.RESULTS:Out of twenty three studies we initially retrieved in our search,only nine studies met the eligibility criteria of being controlled trials within geriatrics.The laxatives examined in the nine studies were senna,lactulose,sorbital,polyethylene glycol(PEG),lubiprostone,linaclotide,and prucalopride.In those studies,senna combinations had a higher efficacy than sorbitol or lactulose as well as,a very good adverse effect profile.PEG was also shown to be safe and effective in geriatric population.Furthermore,it has been shown that PEG is as safe in geriatrics as in general population.New agents like lubiprostone and prucalopride show promising results but the data about these agents in geriatrics are still limited which warrant further investigation.CONCLUSION:Senna combinations and PEG appear to have a more favorable profile over the other traditionally used laxatives in elderly patients with constipation.

FDA连线

FDA批准首个生物防卫产品上市；FDA批准马来酸罗格列酮＋格列美脲的复方制剂；FDA批准辉瑞公司重组人胰岛素干粉吸入剂Exubera；FDA批准辉瑞公司抗真菌药阿尼芬净上市；FDA批准lubiprostone治疗成人慢性特发性便秘。

04012 06年1月美FDA批准的NDA

美国FDA于2006年1月份批准了下述几件NDA申请。它们是Sutent、RotaTeq、lubiprostone和ranolazine。